HUMAN EMBRYOLOGY: Teratogens & Parturition

Timing of Birth Defects:

• Most prominent between 3 – 8 weeks

• Continues throughout development

• Prior to 3 weeks, the disruptions are so severe that miscarriage occurs

Do birth defects only occur during the 3-8 week window?

No, birth defects can continue throughout development, though the 3-8 week period is most prominent

Why is the 3-8 week period particularly critical for birth defects?

This is when gastrulation and neurulation occur and most organ systems are being established, making the embryo especially vulnerable to developmental disruptions

When does the bilaminar embryo develop?

2-3 weeks of development

What key structures form at 18-19 days of development?

• Primitive streak

• Oropharyngeal membrane

• Cloacal membrane

What is the significance of angiogenic cells during early development?

They migrate from the primitive streak to the anterior lateral plate, contributing to early cardiovascular development

What is the primitive streak?

A linear band of cells that forms in the early embryo (18-19 days), marking the future longitudinal axis of the embryo and serving as a site for cell migration during gastrulation

What is the relationship between the primitive streak and primitive heart field?

The primitive streak gives rise to angiogenic cells that migrate to form the primitive heart field in the anterior lateral plate

What is the developmental sequence of early heart formation?

1. Primitive streak forms

2. Angiogenic cells migrate from primitive streak

3. These cells move to anterior lateral plate to establish primitive heart field

4. Primitive heart field then develops into early cardiac structures

When does the primitive heart field begin to form relative to the primitive streak?

The primitive streak appears at 18-19 days, with angiogenic cells then migrating to form the primitive heart field shortly after

What key cardiovascular structures are present at 3 weeks?

Primitive heart field

Blood islands with myoblasts

What is the timing relationship between the neural plate and primitive heart field development?

Both structures begin to form around 3 weeks

What is cardiac looping?

A process during the third week (days 22-24) where the primitive heart tube bends and twists to establish the basic chambered structure of the heart

When does the first primitive heart beat begin?

During the 3rd week

When does the neural tube form?

3rd week

What is the sequence of neural tube development from day 19 to 20?

Day 19: Neural plate stage

Day 20: Neural folds and neural groove form

(Part of process where flat neural plate will fold into neural tube)

When does somite formation begin relative to neural tube development?

During the third week, appearing around day 20

What is gastrulation?

A process during the third week where the bilaminar embryo develops into a trilaminar embryo through the formation of the three germ layers (ectoderm, mesoderm, endoderm)

What is the fundamental milestone at 8 weeks of development?

• Embryo has acquired human form

• All organ systems have begun developing

• Marks transition from embryonic to fetal development

How does growth progress from 5-8 weeks? (Include CRL)

• 5 weeks: CRL 9.8 mm (basic structures forming)

• 6 weeks: CRL 13 mm (continued development)

• 8 weeks: CRL 25 mm (recognizably human form)

What's the key conceptual difference between embryonic and fetal periods?

• Embryonic period (first 8 weeks): Foundation and basic structure formation

• Fetal period (after 8 weeks): Growth and maturation of existing structures

What's the "big picture" concept of the first 8 weeks of development?

First 5 weeks: Laying down basic body plan and organ foundations

Weeks 5-8: Refinement of structures and acquiring human form

Result: All major structures present, ready for growth and maturation

What are two key advantages of ultrasound for fetal evaluation?

1. Non-invasive

2. Non-isotopic (no radiation exposure)

What are two main diagnostic categories that ultrasound can evaluate?

1. Normal anatomy/development

2. Anatomical anomalies/birth defects

What can ultrasound measure to assess fetal growth rate?

• Crown-rump (CR) length

• Bi-parietal diameter of the skull

• Abdominal circumference

• Femur length

How is ultrasound used in amniocentesis?

It guides the needle placement during the procedure, making it safer and more accurate

The position of the aspiration needle during ______ is next to the fetal skull in the amniotic cavity.

amniocentesis

Amniocentesis is not usually performed before ______ of gestation, since 20-30 mL of amniotic fluid is withdrawn. The risk of fetal loss is around ________ overall, but may be less for highly skilled individuals and centers.

14 weeks

1 in 300-500

What are the many different types of teratgoens?

• Infectious agents

• Physical agents

• Chemical agents

• Hormones

Teratogens:

Examples of infectious agents

• Rubella virus

• Cytomegalovirus

• Toxoplasmosis

Infectious agents:

_______ was formerly a major problem, but is now well-controlled by a vaccine

Rubella

Infectious agents:

________ is a serious threat. Mothers are often asymptomatic, but newborns can be seriously ill or die from defects apparent at birth or may be delayed until later.

Cytomegalovirus

Infectious agents:

_________ causes brain defects; symptoms may first appear at birth or later.

Toxoplasmosis

Why should pregnant women avoid changing cat litter?

Cat litter/feces can contain Toxoplasma gondii, which causes toxoplasmosis. This can lead to serious congenital malformations including:

• Hydrocephalus

• Cerebral calcifications

• Microphthalmia

Teratogens:

Examples of physical agents

X-rays

Physical agents

__________: is a potent teratogen, producing almost any type of birth defect depending upon the dose and stage of development.

Ionizing radiation

Teratogens:

Examples of chemical agents

Thalidomide

Alcohol

Lead

What cogenital malformations are associated with the chemical agent Thalidomide?

Limb defects

Heart malformations

What is Thalidomide and what was its historical medical use?

A drug used as an anti-nausea/sleep aid in Europe in the 1960s.

Caused major birth defects but was prevented from entering US market.

What birth defects were caused by Thalidomide?

Amelia/meromelia (loss of limbs)

Who prevented Thalidomide from being approved in the United States?

Frances Oldham Kelsey (FDA reviewer)

What are the characteristic facial features of Fetal Alcohol Syndrome (FAS)?

Small head

Small eye openings

Epicanthal folds

Flat midface

Low nasal bridge

Short nose

Smooth philtrum

Thin upper lip

Underdeveloped jaw

What is the difference between FAS and FASD?

FASD (Fetal Alcohol Spectrum Disorder) is the umbrella term that describes the range of effects from prenatal alcohol exposure.

FAS is the most severe form of FASD, with characteristic facial features, growth problems, and central nervous system problems.

What is the known safe amount of alcohol during pregnancy?

Complete abstinence is recommended to prevent FASD

How common is Fetal Alcohol Syndrome?

Affects as many as 1 in 100 live births

Chemical agents:

What are the potential risks associated with Tylenol (acetaminophen) use during pregnancy?

Asthma

Attention Deficit Disorder (ADHD)

Note: Mechanism not fully understood, considered small risk (ongoing research)

What is the generic name for Tylenol?

Acetaminophen

Teratogens:

Examples of Hormones

Diethylstilbestrol (DES)

Hormones:

Diethylstilbestrol (DES) is a synthetic estrogen that was used to ________. Women exposed to DES in utero had higher incidences of ________ of the vagina and cervix as well as higher incidences of ______ of the uterine tubes, uterus, and upper vagina. Male embryos exposed in utero were also affected, though less severely.

prevent abortion

carcinomas

malformations

Hormones:

___________ interfere with the interaction of estrogen with its receptors and cause developmental disruptions. Today, environmental estrogens largely derived from industrial chemicals and pesticides are becoming more prevalent and can affect many aspects of sexual development, ____________, in males and females.

Endocrine disruptors

both anatomical and behavioral

*Note: Area of interest but not enough data yet

Lack of Proper Nutrition:

A deficiency in _______ often results in neural tube defects (spina bifida)

folic acid

Folic acid (400 ug daily) reduces occurrence of _________ by 50-70% if taken by women of child-bearing age.

neural tube defects (spina bifida)

Normal newborn size at delivery ranges from ___________

2,500 to 4000 g (6-9 lbs)

Normal newborn CRL (Crown-Rump-Length) at delivery is ________

51 cm (20 inches)

________________ refers to a birth weight of < 2500 g, regardless of gestational age (includes pre-term infants).

Low birth weight (LBW)

In contrast, intrauterine growth restriction (IUGR) and small for gestational age (SGA) take into account ____________.

gestational age

_________________ applies to infants who do not attain their optimal intrauterine growth, are pathologically small, and are at risk for poor outcomes.

Intrauterine growth restriction (IUGR)

_____________ infants have birth weight below the 10th percentile for their gestational age. They may have IUGR or they may be constitutionally small and still healthy. The challenge is to distinguish between the two so as not to subject healthy infants to unnecessary high risk protocols for IUGR.

Small for gestational age (SGA)

Parturition: Changes in circulation at birth

1. Functional closure of _________ within a few minutes by smooth muscle contraction in their walls. Actual obliteration of the lumen by fibrous proliferation takes _______; vessel remnants become median umbilical ligaments.

umbilical arteries

2-3 months

Parturition: Changes in circulation at birth

2. Closure of the _____________ occurs shortly after that of the umbilical arteries. Blood from the _____ may enter the newborn for some time after birth. The umbilical vein forms the ligamentum teres hepatis, and the ductus venosus forms the ligamentum venosum in the liver.

umbilical vein and ductus venosus

placenta

Parturition: Changes in circulation at birth

3. Closure of the _______ by contraction of its muscular wall occurs immediately after birth. Complete anatomical obliteration takes ______, with the remnant becoming the ligamentum arteriosum.

ductus arteriosus

1 - 3 months

Parturition: Changes in circulation at birth

4. Closure of the ______ is caused by increased pressure in the left atrium along with decreased pressure in the right atrium. The _____ compresses the septum primum against the septum secundum. During the first days of life, this closure is reversible, and crying can create a shunt from right to left that accounts for cyanotic periods in the newborn. Fusion of the two septa occurs within a year, although in __ of individuals complete anatomical closure may never occur.

foramen ovale

first breath

20%

What does APGAR stand for and who developed it?

Virginia Apgar in 1952

A = Appearance

P = Pulse

G = Grimace

A = Activity

R = Respiration

Note: This is a backronym (acronym created after the fact)

When is the APGAR score assessed?

At 1 and 5 minutes after birth

APGAR Score:

Each criteria scores ___ for a total of 10 points

0-2

What are the scoring ranges for APGAR and their interpretations?

7-10 = normal

4-6 = low

0-3 = critically low

Total possible score: 10 points (0-2 points for each of 5 criteria)

Who first described what we now know as Fetal Alcohol Spectrum Disorder (FASD) and when?

Stephen Hales of Corpus Christi College, Cambridge, in 1751

Note: Though the formal description wasn't made until the 1970s

What was Hales' groundbreaking insight about the cause of alcohol-related birth problems?

He recognized that alcohol itself was doing the damage, contrary to the prevailing view that it was a weakness in the mothers that caused both their drinking and their children's problems

*He made this observation over 200 years before FASD was formally described in the 1970s, showing remarkable insight into the direct causal relationship between maternal alcohol consumption and fetal harm.